DESCRIPTION: (Applicant's Abstract) The standard treatment for muscle- invasive bladder cancer is cystectomy. Though often curative, this is a mutilating procedure and its effects on quality of life are unacceptable to many patients. Clinical studies have shown that patients with early muscle-invasive bladder cancer whose tumors bear mutations of p53, RB, or both, have a higher rate of progression and decreased survival following cystectomy alone. An objective of ongoing clinical research is to optimize the use of chemotherapy, surgery, and novel therapeutic modalities in treatment of patients with muscle-invasive tumors to improve the prognosis of those that have p53 or RB mutations and to develop gene therapy for bladder cancer in the context of a Phase 1 clinical trial of the replication defective adenoviral vector Ad-p53, administered by intravesical instillation in patients with locally advanced bladder cancer. The specific aims are as follows: 1) conduct a Phase 1 clinical trial of intravesically administered Ad-p53 in patients with muscle-invasive bladder cancer; 2) demonstrate infection of tumor cells and expression of p53 gene by adenoviral vector through intravesical administration; 3) characterize the in vivo effect of p53 gene transfer on apoptosis in bladder cancer; 4) investigate effect of p53 gene transfer on regulation of angiogenesis in bladder cancer. Upon completion of the Phase 1 trial and correlative laboratory studies described, the applicant will develop a Phase II study of combined chemotherapy and Ad-p53 in patients with early muscle-invasive bladder cancer who have failed an initial attempt at organ preservation.